RESUMO
In the perfused rat liver, administration of glucagon causes a hyperpolarization of the liver cell membrane and increases gluconeogenesis. Insulin, a hormone which is known to antagonize the effect of glucagon on gluconeogenesis also blocks the hyperpolarizing effect of glucagon. Because of this inhibitory effect of insulin of the glucagon-evoked hyperpolarization, a systematic study of possible correlation between changes in membrane potential and gluconeogenesis was undertaken. The membrane potential was changed by valinomycin, tetracaine, or by varying the ionic composition of the perfusate. A highly significant correlation between changes in membrane potential and the rate of gluconeogenesis was noticed. The possibility was raised that changes in membrane potential might exert an influence on metabolic process by a yet unknown mechanism.
Assuntos
Membrana Celular/fisiologia , Glucagon/farmacologia , Gluconeogênese/efeitos dos fármacos , Insulina/farmacologia , Fígado/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Fígado/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , RatosAssuntos
AMP Cíclico/farmacologia , GMP Cíclico , Glucagon/farmacologia , Fígado/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potássio/metabolismo , Sódio/metabolismo , Glândulas Suprarrenais/fisiologia , Adrenalectomia , Animais , Transporte Biológico/efeitos dos fármacos , Dexametasona/farmacologia , Masculino , Perfusão , Ratos , Fatores de TempoAssuntos
Fígado/fisiologia , Potenciais da Membrana/efeitos dos fármacos , Acetatos/farmacologia , Alanina/farmacologia , Ácidos Aminoisobutíricos/farmacologia , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , AMP Cíclico/farmacologia , Frutose/farmacologia , Galactose/farmacologia , Glucagon/farmacologia , Glucose/farmacologia , Lactatos/farmacologia , Fígado/efeitos dos fármacos , Lisina/farmacologia , Masculino , Ouabaína/farmacologia , Ácidos Palmíticos/farmacologia , Perfusão , Piruvatos/farmacologia , RatosRESUMO
The hypothesis that cocaine has Class I-type antiarrhythmic drug effects was tested in tissues isolated from rabbit heart with standard microelectrode methods. Propranolol (1 microM) was used to block beta-adrenergic effects. The actions of cocaine on cellular electrophysiology were concentration- and time-dependent and were reversible. In paced right atrial (RA) and right ventricular papillary (RVP) tissues, cocaine produced a profound prolongation of the effective refractory period (ERP) assessed by either premature stimulation or minimum pacing interval. ERP was increased up to eightfold in RA tissue and doubled in RVP tissue by 60 microM cocaine. This concentration of cocaine depressed action potential phase 0 depolarization 80% in RA tissue and 53% in RVP tissue but had no effect on resting membrane potentials. Automaticity was moderately depressed in sinus node (34% decrease in rate) but not in tricuspid valve cells. Phase 0 depolarization was not altered in these spontaneously active slow-response cells. Repolarization was depressed in RA, tricuspid valve, and sinus node cells leading to a twofold increase in action potential duration during exposure to cocaine. Evidence from the effects on cellular action potentials suggests that cocaine affects both fast Na+ channels and repolarizing K+ but not Ca2+ channels. We conclude that cocaine has Class I-type activity and the effects on ERP are extreme.
Assuntos
Cocaína/farmacologia , Coração/efeitos dos fármacos , Miocárdio/citologia , Potenciais de Ação/efeitos dos fármacos , Animais , Estimulação Cardíaca Artificial , Coração/fisiologia , Átrios do Coração , Masculino , Músculos Papilares/citologia , Músculos Papilares/efeitos dos fármacos , Músculos Papilares/fisiologia , Propranolol/farmacologia , Coelhos , Nó Sinoatrial/citologia , Nó Sinoatrial/fisiologia , Valva Tricúspide/citologia , Valva Tricúspide/fisiologiaRESUMO
1. The action of Ca on membrane excitability and synaptic transmission at motoneurones of the isolated spinal cord of the frog has been studied.2. Impulse propagation along presynaptic fibres was unaffected by [Ca] in the range of 0-10 mM in the presence of 1 mM-Mg.3. Motoneurone membrane excitability was within normal ranges when the cord was bathed in low or 0 Ca solutions containing 1 mM-Mg but was depressed in 5 or 10 mM-Ca solutions.4. Spontaneous miniature synaptic potentials were recorded in the presence of tetrodotoxin. The frequencies were reduced but not abolished in the absence of bath Ca, but were increased greater than twofold in 5 or 10 mM-Ca in comparison to those in normal Ringer solution (1 mM-Ca).5. Iontophoretic application of Ca both near to and remotely from the intracellular recording site (presumably in the soma) caused facilitation of elicited post-synaptic potentials.6. It is concluded that the action of Ca at these central synapses is identical to that described at the neuromuscular junction.
Assuntos
Cálcio/farmacologia , Neurônios Motores/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Anuros , Depressão Química , Eletrofisiologia , Iontoforese , Magnésio , Potenciais da Membrana/efeitos dos fármacos , Neurônios Motores/fisiologia , Rana pipiens , Medula Espinal/fisiologia , Sinapses/efeitos dos fármacos , Tetrodotoxina/farmacologiaRESUMO
Intracellular microelectrode recordings of acinar cell membrane potentials were made from fragments of the rat lacrimal gland superfused in vitro. The average resting membrane potential was -45 mV. Carbachol and epinephrine produced virtually identical membrane potential changes consisting of an initial hyperpolarization (1 mV), lasting approximately 7 sec, followed by a depolarization of approximately 12 mV. The membrane potential generally returned to prestimulation levels after 2 min of exposure to agonist. The responses to carbachol and epinephrine were blocked by atropine and phentolamine, respectively. Superfusion with media lacking Ca or Cl reduced significantly both the resting membrane potential and the agonist-induced depolarization. The hyperpolarization was increased significantly in the absence of Ca and generally prolonged in the absence of Cl. Superfusion with 10 mM Co had no effect on either the resting membrane potential or the agonist-induced membrane potential changes. The hyperpolarization initiated by agonist was significantly enhanced during superfusion with low K, ouabain or amiloride while the depolarization was significantly reduced during superfusion with low K, amiloride or low Na. Resting membrane potentials during superfusion with low K, amiloride or low Na were not significantly different from control, whereas ouabain caused a small depolarization. It is concluded that muscarinic or alpha adrenergic receptor stimulation initiates a membrane potential change characterized by a hyperpolarization, due to an increased in membrane permeability to K, followed by a depolarization due to an increase in membrane permeability to Na.
Assuntos
Carbacol/farmacologia , Epinefrina/farmacologia , Aparelho Lacrimal/efeitos dos fármacos , Animais , Eletrólitos/metabolismo , Técnicas In Vitro , Aparelho Lacrimal/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , RatosRESUMO
A test for diminished neuromuscular function in animals with experimental autoimmune myasthenia gravis is described. Within minutes following an injection of gallamine triethiodide, mice exhibit a dramatic yet transient response which is dose-dependent. Mice previously inoculated with acetylcholine receptor are approximately twice as sensitive to gallamine as normal mice. Positive results have been found in over 80% of receptor-inoculated BALB/c mice and in 94% of C57Bl/6 mice.
Assuntos
Doenças Autoimunes/fisiopatologia , Trietiodeto de Galamina , Miastenia Gravis/fisiopatologia , Receptores Colinérgicos/fisiologia , Animais , Autoanticorpos/biossíntese , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrofisiologia , Teste de Esforço , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neurônios Motores/fisiologia , Tempo de Reação , Receptores Colinérgicos/administração & dosagem , Receptores Colinérgicos/imunologiaRESUMO
The principally active hemolytic toxin (cardiotoxin) previously purified from the venom of the Thailand cobra, Naja naja siamensis, was shown to produce spontaneous twitching, contractures and membrane depolarization in sartorius muscles from the frog, Rana pipiens. Spontaneous twitching, observed at concentrations greater than 0.1 uM was completely abolished by addition of tetrodotoxin and not affected by d-tubocurarine. Dose and time dependent membrane depolarization of muscle fibers was observed to occur within 10-30 min at 0.2 to 1.0 uM concentrations of the toxin. These observations, taken together with an amino acid analysis characteristic of previously described cobra venom cardiotoxins, characterized this hemolytic toxin as a cardiotoxin. In the absence of EDTA the initial velocities of erythrocyte hemolysis for this toxin showed a sigmoidal concentration dependence which became hyperbolic in the presence of EDTA. The largest increases in hemolysis rates on addition of 1 mM EDTA were observed at low toxin concentrations. In the presence of EDTA extracellular and membrane associated divalent cations are complexed, thus alleviating their competition with toxin for binding to the membrane, a key and apparently rate-determining initial step which leads to hemolysis. In the presence of EDTA hemolysis rates increased linearly at low toxin concentration and reached an extrapolated maximum value at toxin concentrations at which, given its molecular dimensions, there are just sufficient toxin molecules to cover the entire membrane surface area provided by the erythrocytes.